Mercaptopurine
Encyclopedia
Mercaptopurine is an immunosuppressive drug
.
It is a thiopurine
.
, pediatric non-Hodgkin's lymphoma, polycythemia vera
, psoriatic arthritis
, and inflammatory bowel disease
(such as Crohn's disease
and ulcerative colitis
).
It has demonstrated some in vitro effectiveness against Mycobacterium paratuberculosis.
and DNA
. Mercaptopurine interferes with nucleotide
interconversion and glycoprotein synthesis.
s of taking mercaptopurine might include diarrhea, nausea, vomiting, loss of appetite, fatigue, stomach/abdominal pain, weakness, skin rash
, darkening of the skin, or hair loss. Serious adverse reactions include mouth sores, fever
, sore throat
, easy bruising or bleeding, pinpoint red spots on the skin, yellowing of eyes or skin, dark urine
, and painful or difficult urination. Unlikely but serious side-effects include: black or tarry stools
(melena
), bloody stools, and bloody urine
.
Symptoms of allergic reaction to mercaptopurine include rash
, itching, swelling
, dizziness
, trouble breathing
, and pancreatitis
.
Mercaptopurine causes myelosuppression, suppressing the production of white blood cell
s and red blood cell
s. It may be toxic to bone marrow
. Weekly blood counts are recommended for patients on mercaptopurine. The patient should stop taking the medication at least temporarily if there is an unexplained, abnormally large drop in white blood cell count, or any other blood count.
Patients exhibiting myelosuppression or bone marrow
toxicity should be tested for thiopurine methyltransferase
(TPMT) enzyme deficiency. Patients with TPMT deficiency are much more likely to develop dangerous myelosuppression. In such patients, it may be possible to continue using mercaptopurine, but at a lower dose.
, the enzyme that breaks down mercaptopurine. Those taking allopurinol
(often used to prevent gout) are at risk for mercaptopurine toxicity. The dose should be reduced or allopurinol should be discontinued.
s and vaccination
s. It is also recommended that, while on the drug, one should avoid those having recently received oral polio vaccine.
This drug is traditionally not recommended during pregnancy, but this issue has been debated, and current evidence indicates that pregnant women on the drug show no increase in fetal abnormalities. However, women receiving mercaptopurine during the first trimester of pregnancy have an increased incidence of miscarriage. Davis et al. 1999 found that mercaptopurine, compared to methotrexate
, was ineffective as a single-agent abortifacient; every woman in the mercaptopurine arm of the study had fetal cardiac activity at follow-up (two weeks later) and was given a suction abortion.
Mercaptopurine causes changes to chromosome
s in animals and humans, though a study in 1990 found that, "while the carcinogenic potential of 6-MP cannot be precluded, it can be only very weak or marginal." Another study in 1999 noted an increased risk of developing leukemia when taking large doses of 6-MP together with other cytotoxic drugs.
Immunosuppressive drug
Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...
.
It is a thiopurine
Thiopurine
The thiopurine drugs are purine antimetabolites widely used in the treatment of acute lymphoblastic leukemia, autoimmune disorders , and organ transplant recipients.Metabolism is catalyzed by S-methyltransferase....
.
Uses
It is used to treat leukemiaLeukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
, pediatric non-Hodgkin's lymphoma, polycythemia vera
Polycythemia vera
Polycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health concerns associated with polycythemia vera are caused by the blood being thicker as a result of the...
, psoriatic arthritis
Psoriatic arthritis
Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...
, and inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
(such as Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
and ulcerative colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
).
It has demonstrated some in vitro effectiveness against Mycobacterium paratuberculosis.
Mechanisms of action
6-MP ribonucleotide inhibits purine nucleotide synthesis and metabolism. This alters the synthesis and function of RNARNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
and DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. Mercaptopurine interferes with nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
interconversion and glycoprotein synthesis.
Adverse reactions
Some of the adverse reactionAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s of taking mercaptopurine might include diarrhea, nausea, vomiting, loss of appetite, fatigue, stomach/abdominal pain, weakness, skin rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
, darkening of the skin, or hair loss. Serious adverse reactions include mouth sores, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, sore throat
Sore throat
A sore throat or throat pain is a common physical symptom usually caused by acute pharyngitis, or throat inflammation, though it also occurs in a number of other situations, such as post trauma and in diphtheria. It can cause mild to extreme pain....
, easy bruising or bleeding, pinpoint red spots on the skin, yellowing of eyes or skin, dark urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, and painful or difficult urination. Unlikely but serious side-effects include: black or tarry stools
Human feces
Human feces , also known as a stool, is the waste product of the human digestive system including bacteria. It varies significantly in appearance, according to the state of the digestive system, diet and general health....
(melena
Melena
In medicine, melena or melaena refers to the black, "tarry" feces that are associated with gastrointestinal hemorrhage. The black color is caused by oxidation of the iron in hemoglobin during its passage through the ileum and colon.-Melena vs...
), bloody stools, and bloody urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
.
Symptoms of allergic reaction to mercaptopurine include rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
, itching, swelling
Swelling (medical)
In medical parlance, swelling is the transient enlargement or protuberance in the body and may include tumors. According to cause, it may be congenital, traumatic, inflammatory, neoplastic or miscellaneous....
, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, trouble breathing
Breathing
Breathing is the process that moves air in and out of the lungs. Aerobic organisms require oxygen to release energy via respiration, in the form of the metabolism of energy-rich molecules such as glucose. Breathing is only one process that delivers oxygen to where it is needed in the body and...
, and pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
.
Mercaptopurine causes myelosuppression, suppressing the production of white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s and red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s. It may be toxic to bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
. Weekly blood counts are recommended for patients on mercaptopurine. The patient should stop taking the medication at least temporarily if there is an unexplained, abnormally large drop in white blood cell count, or any other blood count.
Patients exhibiting myelosuppression or bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
toxicity should be tested for thiopurine methyltransferase
Thiopurine methyltransferase
Thiopurine methyltransferase or thiopurine S-methyltransferase is an enzyme that methylates thiopurine compounds. The methyl donor is S-adenosyl-L-methionine, which is converted to S-adenosyl-L-homocysteine....
(TPMT) enzyme deficiency. Patients with TPMT deficiency are much more likely to develop dangerous myelosuppression. In such patients, it may be possible to continue using mercaptopurine, but at a lower dose.
Drug interactions
Allopurinol inhibits xanthine oxidaseXanthine oxidase
Xanthine oxidase Xanthine oxidase Xanthine oxidase (XO (sometimes 'XAO'), a form of xanthine oxidoreductase that generates reactive oxygen species. Is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid...
, the enzyme that breaks down mercaptopurine. Those taking allopurinol
Allopurinol
Allopurinol is a drug used primarily to treat hyperuricemia and its complications, including chronic gout.- Mechanism of action :...
(often used to prevent gout) are at risk for mercaptopurine toxicity. The dose should be reduced or allopurinol should be discontinued.
Precautions
Mercaptopurine can lower the body's ability to fight off infection. Those taking mercaptopurine should get permission from a doctor in order to receive immunizationImmunization
Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an agent ....
s and vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
s. It is also recommended that, while on the drug, one should avoid those having recently received oral polio vaccine.
This drug is traditionally not recommended during pregnancy, but this issue has been debated, and current evidence indicates that pregnant women on the drug show no increase in fetal abnormalities. However, women receiving mercaptopurine during the first trimester of pregnancy have an increased incidence of miscarriage. Davis et al. 1999 found that mercaptopurine, compared to methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, was ineffective as a single-agent abortifacient; every woman in the mercaptopurine arm of the study had fetal cardiac activity at follow-up (two weeks later) and was given a suction abortion.
Mercaptopurine causes changes to chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s in animals and humans, though a study in 1990 found that, "while the carcinogenic potential of 6-MP cannot be precluded, it can be only very weak or marginal." Another study in 1999 noted an increased risk of developing leukemia when taking large doses of 6-MP together with other cytotoxic drugs.